Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication.
Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication.
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口蹄疫病毒感染抑制LGP2蛋白表达，从而加剧炎症反应并促进病毒复制。
DOI：
10.1038/cddis.2017.170
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发表时间：
2017-04-13
影响因子：
9
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Zhu Z;Li C;Du X;Wang G;Cao W;Yang F;Feng H;Zhang X;Shi Z;Liu H;Tian H;Li D;Zhang K;Liu X;Zheng H
先天免疫蛋白LGP 2（遗传学和生理学实验室2）在口蹄疫病毒感染细胞中的作用仍然未知。在这里，我们证明了LGP 2在FMDV感染过程中的抗病毒作用。FMDV感染可诱导LGP 2 mRNA表达，但蛋白表达降低。过表达LGP 2可抑制口蹄疫病毒的复制，并显著抑制病毒感染细胞的炎症反应。LGP 2的N-末端DExDc和C-末端调节结构域区域是LGP 2介导的抗FMDV活性所必需的。LGP 2对RNA识别的破坏被认为完全消除了LGP 2介导的抗FMDV的抗病毒活性。确定FMDV前导蛋白（Lpro）以及3Cpro和2B蛋白具有诱导LGP 2蛋白表达降低的能力。2B诱导的LGP 2的减少不依赖于真核翻译起始因子4 γ的切割，并且蛋白酶体、溶酶体或半胱天冬酶依赖性途径不参与该过程。101-154的C-末端氨基酸对于2B诱导的LGP 2减少和炎症反应上调是必需的。LGP 2和2B之间存在直接相互作用。我们的研究结果描述了LGP 2对FMDV的抗病毒作用和一种新的由2B蛋白介导的FMDV拮抗机制。
The role of the innate immune protein LGP2 (laboratory of genetics and physiology 2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression but reduced protein expression. Overexpression of LGP2 suppressed FMDV replication, and the inflammatory response was significantly inhibited by LGP2 in virus-infected cells. The N-terminal DExDc and the C-terminal regulatory domain regions of LGP2 were essential for LGP2-mediated antiviral activity against FMDV. Disruption of RNA recognition by LGP2 is suggested to abolish completely LGP2-mediated antiviral activity against FMDV. FMDV leader protein (Lpro), as well as the 3Cpro and 2B proteins were determined to possess the ability to induce reduction of LGP2 protein expression. 2B-induced reduction of LGP2 was independent of cleavage of eukaryotic translation initiation factor 4 gamma; and the proteasomes, lysosomes or caspase-dependent pathways were not involved in this process. The C-terminal amino acids of 101–154 were essential for 2B-induced reduction of LGP2 and upregulation of inflammatory response. Direct interaction was demonstrated between LGP2 and 2B. Our results describe the antiviral role of LGP2 against FMDV and a novel antagonistic mechanism of FMDV that is mediated by 2B protein.